Electrolysis has been used for minimally invasive tissue ablation since the early 1800's. The process of electrolysis occurs at the electrode surfaces for electrodes submerged in an ionic conducting media. New chemical species are generated at the interface of the electrodes as a result of the electric potential driven transfer between electrons and ions or atoms. The various chemical species produced near the electrodes diffuse away in a process driven by differences in electrochemical potential. In physiological solutions these chemical reactions also yield changes in pH, resulting in an acidic region near the anode and a basic region near the cathode. Tissue ablation is driven by two factors: a cytotoxic environment developing due to local changes in pH, as well as the presence of some of the new chemical species formed during electrolysis. Electrolysis is a chemical ablation mechanism, and the extent of ablation is a function of the concentration of the chemical species and the exposure time to these chemicals. The total amount of electrolytic products generated during electrolysis is related to the charge delivered during the process, and therefore the total charge is used as a quantitative measure for the extent of electrolysis.
Over the last two decades, substantial research has been done on tissue ablation by products of the electrolysis process in ionic aqueous solutions, including cell and animal experiments, mathematical modeling, and clinical work. In the contemporary literature, electrolytic ablation using products of electrolysis generated from tissue ions and molecules is sometimes referred to as Electro-Chemical Therapy (EChT). Unless specifically stated otherwise, the terms “the products of electrolysis” and “electrolysis products” refer to products generated from the transfer and removal of electrons to ions and molecules in an ionic aqueous solution and involve only the components of the aqueous solution or tissue as an aqueous solution. Unless stated otherwise, the process of electrolysis implies the use of inert electrodes that do not participate in the process of electrolysis except as a source or sink of electrons or as catalysts. This is also how electrolysis is defined in EChT. As used herein, “electrolysis” or “electrolytic” refers to the process of electrolysis and the products of electrolysis as defined above. Electrolytic ablation has been shown to exhibit several unique attributes. First, due to the chemical nature of the ablation process, the diffusion of chemical species in the tissue and the rate of chemical reactions dominate the time scale of the procedure. Second, the chemical products at the anode differ from those formed at the cathode, thus resulting in distinct mechanisms of ablation. Finally, electro-osmotic forces drive the migration of water from the anode to the cathode, further magnifying the contrasting physiological effects at the electrode surfaces. From an operational standpoint electrolysis may use very low voltages and currents, providing advantages relative to other ablation techniques, e.g. reduced instrumentation complexity. It is, however, a lengthy procedure, controlled by the process of diffusion and the need for high concentrations of electrolytically-produced ablative chemical species.
Electroporation also harnesses an electricity-induced phenomenon; it differs from electrolysis by employing a different set of biophysical principles. The bioelectric phenomenon of electroporation is characterized by the permeabilization of the cell membrane through the application of very brief, high-magnitude electric field pulses. The extent of membrane permeabilization is a function of the electric field strength. Electroporation can be used to produce reversible pores, defects, in the lipid bilayer, allowing for the introduction of molecules such as genes and drugs into cells. This is generally referred to as “reversible electroporation” The electric parameters, however, can be designed to produce irreversible defects in the cell membrane, resulting in a cell membrane that does not reseal after the field is removed. This is referred to as “irreversible electroporation”. Reversible electroporation techniques have been combined with anticancer drugs such as bleomycin to target cancerous tissues for successful clinical use in the field of electrochemotherapy. Reversible electroporation is also used in other medical and biotechnological applications, including transfection and introduction of molecules such as siRNA into cells that survive the permeabilization process. Electroporation specifically targets the cell membrane through the application of an electric field that develops instantaneously. Irreversible electroporation may be used for tissue ablation.